120 do-co paris suppinf 2012 04 02

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Pd-Catalyzed Domino Carbonylative / Decarboxylative Allylation: An Easy and Selective Monoallylation of Ketones

Steven Giboulot,a Frédéric Liron,a,* Guillaume Prestat,a,1 Benoit Wahl,b Mathieu Sauthier,b Yves Castanet,b André Mortreux b and Giovanni Poli a,*

a UPMC, IPCM, UMR CNRS 7201, 4 place Jussieu, case 183, F-75252 Paris Cedex 05, France; Tel: (+)33 1 44 27 41 14; E-mail: [email protected] b Unité de Catalyse et de Chimie du Solide, UCCS, UMR CNRS 8181, Bât. C7, Cité Scientifique, B. P. 90108, 59652 Villeneuve d'Ascq Cedex, France; E-mail: [email protected]

Supplementary Information

1 Present address: Université Paris Descartes, UMR 8601 CNRS, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints-Pères, 75006 Paris, France

Electronic Supplementary Material (ESI) for Chemical CommunicationsThis journal is © The Royal Society of Chemistry 2012

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Contents

I. Experimental Section ..................................................................................................... 4

General instrumentation: ............................................................................................... 4

Atmospheric pressure optimization: .............................................................................. 4

Optimization of the carbonylation step: ........................................................................ 5

Optimization of the Pd-catalyzed decarboxylative allylation step: ............................... 5

Optimization of the pseudo-domino sequence: ............................................................. 6

Optimization of the pressure: ........................................................................................ 6

Ligands screening: ......................................................................................................... 7

II. Characterization: ........................................................................................................... 8

Allyl 3-oxo-3-phenylpropanoate (3) ..................................................................... 8

Chlorination of ketones: ................................................................................................ 8

4-(2-Chloroacetyl)benzonitrile (1d) ...................................................................... 9

Methyl 4-(2-chloroacetyl)benzoate (1e) ................................................................ 9

2-Chloro-1-p-tolylethanone (1g) ......................................................................... 10

2-Chloro-1-(3-methoxyphenyl)ethanone (1j) ...................................................... 10

2-Chloro-1-(3-fluorophenyl)ethanone (1i) .......................................................... 11

2-Chloro-1-phenylpropan-1-one (1m) ................................................................. 11

Methyl 3-oxo-3-phenylpropanoate (2) ................................................................ 12

Domino Sequence: Pd-catalyzed Carbonylation / Decarboxylative Allylation .......... 12

1-Phenylpent-4-en-1-one (4a) ............................................................................. 13

1-(4-Fluorophenyl)pent-4-en-1-one (4b) ............................................................. 13

1-(4-Chlorophenyl)pent-4-en-1-one (4c) ............................................................ 14

4-Pent-4-enoylbenzonitrile (4d) .......................................................................... 14

Methyl 4-pent-4-enoylbenzoate (4e) ................................................................... 15


3

1-(4-tert-Butylphenyl)pent-4-en-1-one (4f) ........................................................ 16

1-p-Tolyl-pent-4-en-1-one (4g) ........................................................................... 16

1-(4-Methoxyphenyl)pent-4-en-1-one (4h) ......................................................... 17

1-(3-Fluorophenyl)pent-4-en-1-one (4i) .............................................................. 17

1-(3-Methoxyphenyl)pent-4-en-1-one (4j) .......................................................... 18

1-(2,4-Dichlorophenyl)pent-4-en-1-one (4k) ...................................................... 19

1,2-Diphenylpent-4-en-1-one (4l) ....................................................................... 19

4-Methyl-1-phenylpent-4-en-1-one (4p, 4q) ....................................................... 20

4-Methyl-1-phenylpent-4-en-1-one (4r) .............................................................. 21

III. Spectra .......................................................................................................................... 22


4

I. Experimental Section

General instrumentation:

All carbonylation and tandem reactions were carried out under a CO atmosphere.

All other reactions were carried out under an argon atmosphere. Dry solvents were obtained

from a Braun purification system MB SPS-800. Allyl alcohol was distilled and stored under an

argon atmosphere. NMR spectra were recorded (Bruker 400 MHz or Bruker 300 MHz, 1H,

and 101 MHZ, 13C) in CDCl3 (which also provided the lock signal at δ = 7.26 ppm for 1H and

δ = 77.16 ppm for 13C). IR spectra were recorded on a Bruker Tensor 27 apparatus. Silica gel

(40-63 µm) was used for chromatographic purification. TLC plates were visualized under UV

light and spraying with KMnO4 (5 % in water).

Atmospheric pressure optimization:

Catalyst Base Additiveb Products a

PdCl2(PPh3)2 Et3N - 5 (100%)

Pd(dba)2 + dppe Et3N - 5 (19%) + 6 (81%)

PdCl2dppp Et3N - 5 (35%) + 6 (65%)

Pd(dba)2 + dppb Et3N - 5 (72%) + 6 (28%)

Pd(dba)2 + 4 PCy3 Et3N - 5 (27%) + 6 (73%)

Pd(dba)2 + 4 tfp Et3N - 5 (100%)

PdCl2(PPh3)2 NaOAc BnNEt3Br

5 (11%) + a Calculated on the basis of 1H NMR spectrum of the crude product. b 0.2 equiv. of additive is used.


5

Whatever the conditions used under an atmospheric pressure of CO, the desired

product could not be isolated. Optimization of both steps was subsequently undertaken

separately, the carbonylation reaction being carried out under 5 bars of CO.

Optimization of the carbonylation step:

Catalyst Base Additive d T (°C) Products a

PdCl2(PPh3)2 Et3N - 100 2 (16%) + 7 (18%) + 5 (66%)

PdCl2(PPh3)2 Et3N - 130 7 (45%) + 5 (55%)

PdCl2(PPh3)2 Bu3N - 100 2 (11%) + 7 (7%) + 5 (82%)

PdCl2(PPh3)2 DMAN b - 100 2 (49%) c + 7 (6%) + 5 (45%)

PdCl2(PPh3)2 DMAN b BnNEt3Br 100 2 (21%) + 7 (9%) + 5 (70%)

PdCl2dppf DMAN b - 100 2 (16%) + 7 (8%) + 5 (76%)

a calculated on the basis of 1H NMR spectrum of the crude product; b 1,8 bis(dimethylamino)naphtalene ; c isolated

yield: 38%. d 0.2 equiv. of additive is used.

Under 5 bars of CO and using MeOH as the alcohol, up to 38% isolated yield of

the desired methyl β-ketoester 2, was obtained. However, extensive amounts of acetophenone

5 were also isolated, providing a proof for an inefficient carbonylation step.

Optimization of the Pd-catalyzed decarboxylative allylation step:

Catalyst x (mol%) Solvent T (°C) yield (%)a

Pd(dba)2 + 4 PPh3 5 THF 60 64%

Pd(dba)2 + 4 PPh3 5 90 72%

Pd(dba)2 + 4 PPh3 5 Toluene 90 78%

- - Toluene 90 0%


6

a Isolated yields.

The Pd-catalyzed decarboxylative allylation proceeded smoothly, leading to the

desired monoallylated ketone in good yield. In the absence of the palladium catalyst, the

decarboxylative allylation did not take place, showing that the reaction did not occur via a

thermal activation.

Optimization of the pseudo-domino sequence:

Catalyst Base T (°C) yield (%)a

PdCl2(PPh3)2 DMAN b 130 11

PdCl2dppf DMAN b 130 19

Pd(OAc)2 + 4 PPh3 DMAN b 130 20

Pd(OAc)2 + dppb DMAN b 130 12

Pd(OAc)2 + dppf DMAN b 130 1

Pd(OAc)2 + 4 PPh3 Hünig's base 130 8

Pd(OAc)2 + 4 PPh3 NaOAc 130 7 a isolated yields of 4a. The mass balance to 100% is mainly acetophenone. b

1,8 bis(dimethylamino)naphthalene.

Whatever the conditions used under 5 bars of CO, it was not possible to achieve a

yield higher than 20%. The influence of the CO pressure was therefore investigated.

Optimization of the pressure:

PCO (bar) 5 10 15 20 25 30 50 80

yield (%)a 20 7 12 27 18 14 18 0 a Isolated yields of 4a.


7

As previously observed,2 an optimal pressure is observed in the range of 10 to 20

bars. In this case, the optimum is reached at 20 bars, yielding 27% of the monoallylated

ketone.

Ligands screening:

L Yield (%)a

P(t-Bu)3 0

PCy3 13

PPh3 54

PPh2furb 50

PPh(fur)2b 65

trifurylphosphine 76

P(OEt)3 13

dppf 0

XantPhos 56 a Isolated yields of 4a. b fur = 2-furyl.

The screening of ligands showed that the more electron-poor the phosphine, the

more efficient the reaction. Trifurylphosphine led to 76% yield of the desired product.

Phosphites were however inefficient. XantPhos was the only efficient bidentate ligand.

2 A. L. Lapidus, O. L. Eliseev, T. N. Bondarenko, O. E. Sizan, E. G. Ostapenko, and I. P. Beletskaya, Kinetics and Catalysis, 2004, 45, 234.


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II. Characterization:

Allyl 3-oxo-3-phenylpropanoate (3)

A flask was charged with methyl 3-oxo-3-phenylpropanoate 3 (1.45 g, 8.15 mmol,

1 equiv.), DMAP (301.8 mg, 2.45 mmol, 0.3 equiv.) and allyl alcohol (6 mL, 87mmol, 10

equiv.). The reaction was stirred at 90 °C for 3 days. The solution was concentrated in vacuo.

The reaction was hydrolyzed and extracted with ethylacetate. The combined organic layers

were dried over MgSO4 and concentrated in vacuo. The residue was purified by column

chromatography on silica gel (eluent: cyclohexane/AcOEt = 95/5) and yielded 0.875 g (53%)

of the expected product 3 as a colorless oil.

Data for 3: 1H NMR (400 MHz, CDCl3) δ 7.97-7.94 (m, 1H), 7.80-7.77 (m, 1H), 7.62-7.58 (m, 1H), 7.51-

7.40 (m, 2H), 5.90 (ddt, J = 5.7, 10.2, 17.2 Hz, 1H), 5.36-5.20 (m, 2H), 4.65 (dt, J = 1.3, 5.7

Hz, 2H), 4.03 (s, 2H); HRMS (ESI) m/z calcd. for C12H12NaO3 [M + Na+] 227.0673, found

227.0679.

These data are in good agreement with those reported in the literature.3

Chlorination of ketones:

General procedure for the chlorination of ketones: according to the literature: 4

A flask was charged with the substrate (4 mmol), NCS (4 mmol, 1 equiv.), and

PTSA (0.4 mmol, 0.1 equiv.). The reaction mixture was heated to 80 °C overnight. The

reaction was hydrolyzed and extracted with CH2Cl2 (3x10 mL). The combined organic layers

were dried over MgSO4 and concentrated under reduced pressure. The crude reaction mixture

was purified by silica gel column chromatography.

3 J. S. Yadav, B. V. S. Reddy, A. D. Krishna, C. S. Reddy, and A. V. Narsaiah, J. Mol. Catal. A: Chemical, 2007, 261, 93. 4 I. Pravst, M. Zupan, and S. Stavber, Tetrahedron, 2008, 64, 5191.


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4-(2-Chloroacetyl)benzonitrile (1d)

Crude product was purified by column chromatography (eluent:

CH2Cl2/cyclohexane = 3/7). The desired compound was isolated as a white solid (461 mg,

65%).

Data for 1d:

IR (ATR Diamond): 3048, 2928, 2855, 2232, 1706, 1398, 1208, 830 cm-1; 1H NMR (300

MHz, CDCl3) δ 8.08 – 8.06 (m, 2H), 7.84 – 7.81 (m, 2H), 4.68 (s, 2H). 13C NMR (101 MHz,

CDCl3) δ 190.1, 137.2, 132.8, 129.2, 117.7, 117.4, 45.5. HRMS (ESI) m/z calcd. for

C9H6ClNNaO [M + Na+] 202.0030, found 202.0037. M.p. = 90 °C (lit. = 91-95 °C).5


Methyl 4-(2-chloroacetyl)benzoate (1e)


CH2Cl2/cyclohexane = 10/1). The desired compound was isolated as white crystals (535 mg,

63%).

Data for 1e:

IR (ATR Diamond): 3001, 2947, 1704, 1432, 1401, 1279, 1196, 1108, 762 cm-1; 1H NMR

(400 MHz, CDCl3) δ 8.18 – 8.15 (m, 2H), 8.04 –8.01 (m, 2H), 4.73 (s, 2H), 3.97 (s, 3H). 13C

5 G. A. Russell and F. Ros, J. Am. Chem. Soc. 1985, 107, 2506. 6 See: P. R. Olivato, S. A. Guerrero, and R. Rittner, Magnetic Resonance in Chemistry, 1987, 25, 179 for 13C spectrum and: W. Szymanski, C. P. Postema, C. Tarabiono, F. Berthiol, L. Campbell-Verduyn, S. de Wildeman, J. G. de Vries, B. L. Feringa, and D. B. Janssen, Adv. Synth. Catal. 2010, 352, 2111. R. D. Rieke, J. D. Brown and X. Wu, Synth. Commun. 1995, 25, 3923 for 1H spectrum


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NMR (101 MHz, CDCl3) δ 190.6, 165.9, 137.3, 134.6, 130.0, 128.4, 52.5, 45.8. HRMS (ESI)

m/z calcd. for C10H9ClNaO3 [M + Na+] 235.01324, found 235.01325. M.p. = 136 °C.

2-Chloro-1-p-tolylethanone (1g)


CH2Cl2/cyclohexane = 10/1). It afforded the desired compound as a brown solid (539 mg,

80%).

Data for 1g: 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 4.69 (s, 2H),

2.44 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 190.8, 145.1, 131.9, 129.7, 128.7, 46.0, 21.8.

M.p. = 41 °C.


2-Chloro-1-(3-methoxyphenyl)ethanone (1j)


CH2Cl2/cyclohexane = 8/2). It afforded the title compound as a dark red solid (417 mg, 56%).

Data for 1j:


(400 MHz, CDCl3) δ 7.54 – 7.47 (m, 2H), 7.40 (t, J = 7.9 Hz, 1H), 7.16 (ddd, J = 8.2, 2.6, 0.9

Hz, 1H), 4.70 (s, 2H), 3.86 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 190.9, 160.1, 135.6, 129.9,

121.0, 120.5, 112.9, 55.6, 46.2. HRMS (ESI) m/z calcd. for C9H9ClNaO2 [M + Na+]

207.01833, found 207.01836. M.p. = 60 °C.

7 R. N. Ram and T. P. Manoj, J. Org. Chem. 2008, 73, 5633.


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2-Chloro-1-(3-fluorophenyl)ethanone (1i)


CH2Cl2/cyclohexane = 8/2). It afforded the desired compound as a colorless oil (200 mg,

29%).

Data for 1i:

IR (ATR Diamond): 3077, 2946, 1706, 1589, 1484, 1245 cm-1; 1H NMR (400 MHz, CDCl3) δ

7.78 – 7.62 (m, 2H), 7.50 (td, J = 8.0, 5.5 Hz, 1H), 7.33 (tdd, J = 8.2, 2.6, 0.9 Hz, 1H), 4.68 (s,

2H). 13C NMR (101 MHz, CDCl3) δ 190.1, 163.0 (d, J = 249.0 Hz), 136.3 (d, J = 6.4 Hz),

130.7 (d, J = 7.7 Hz), 124.4 (d, J = 3.1 Hz), 121.2 (d, J = 21.4 Hz), 115.5 (d, J = 22.7 Hz),

45.8. HRMS (ESI) m/z calcd. for C8H6ClFNaO [M + Na+] 194.99834, found 194.99804.

2-Chloro-1-phenylpropan-1-one (1m)


CH2Cl2/cyclohexane = 10/1). It delivered the title compound as a yellow oil (572 mg, 85%).

Data for 1m: 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 8.5, 1.3 Hz, 2H), 7.62 – 7.58 (m, 1H), 7.52 – 7.48

(m, 2H), 5.26 (q, J = 6.7 Hz, 1H), 1.75 (d, J = 6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ

193.7, 134.2, 133.8, 129.0, 128.8, 52.9, 20.0.


8 S. Hajra, M. Bhowmick, B. Maji, and D. Sinha, J. Org. Chem. 2007, 72, 4872.


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Methyl 3-oxo-3-phenylpropanoate (2)

Reaction performed with α-chloroacetophenone 1a (309.3 mg, 2.00 mmol, 1.0

equiv.), PdCl2(PPh3)2 (7.4 mg, 0.01 mmol, 0.5 mol%), methanol (5 mL) and 1,8-

bis(dimethylamino)naphthalene (642.2 mg, 3.00 mmol, 1.5 equiv.) at 100 °C for 24 h. The

residue was purified by column chromatography on silica gel (eluent: cyclohexane/AcOEt =

90/10) and yielded 134 mg (38%) of the expected keto-ester 2 as a colorless oil.

Data for 2: 1H NMR (400 MHz, CDCl3) δ 7.95 – 7.93 (m, 2H), 7.61 – 7.57 (m, 1H), 7.50 – 7.46 (m, 2H),

4.00 (s, 2H), 3.75 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 192.4, 168.0, 136.0, 133.9, 128.9,

128.6, 52.5, 45.8. These data are in good agreement with those reported in the literature.9

Domino Sequence: Pd-catalyzed Carbonylation / Decarboxylative Allylation

General procedure for the domino sequence:

The autoclave was charged with α-chloroketone 1a-n (1 mmol, 1 equiv.),

Pd(OAc)2 (0.1 mmol, 0.1 equiv.), tri (2-furyl)phosphine (0.4 mmol, 0.4 equiv.), tributylamine

(1.5 mmol, 1.5 equiv.), allyl alcohol (14.6 mmol, 15 equiv.) and toluene (1.5 mL). The

autoclave was purged with CO and then pressurized (20 bars). The reaction mixture was

warmed to 130 °C for 2 h. After cooling to room temperature, the pressure was carefully

released and the autoclave vented. The reaction was concentrated in vacuo, hydrolyzed and

extracted with diethyl ether. The combined organic layers were dried over MgSO4 and

concentrated in vacuo.

9 T. Taniguchi, Y. Sugiura, H. Zaimoku, and H. Ishibashi, Angew. Chem. Int. Ed. 2010, 49, 10154.


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1-Phenylpent-4-en-1-one (4a)

Reaction performed with α-chloroacetophenone 1a (153.1 mg, 0.99 mmol, 1

equiv.) and allyl alcohol (1 mL, 14.6 mmol, 15 equiv.). The residue was purified by column

chromatography on silica gel (eluent: cyclohexane/AcOEt = 95/5) and yielded 121 mg (76%)

of the expected product 4a as a yellow oil.

Data for 4a:

IR (ATR Diamond): 3062, 2920, 1684, 1597, 1448, 1208, 913, 690 cm-1; 1H NMR (400 MHz,

CDCl3) δ 7.85 – 7.83 (m, 2H), 7.44 – 7.40 (m, 1H), 7.35 – 7.31 (m, 2H), 5.79 (ddt, J = 16.8,

10.2, 6.5 Hz, 1H), 4.97 (dq, J = 17.1, 1.6 Hz, 1H), 4.90 (ddd, J = 10.2, 3.0, 1.3 Hz, 1H), 2.96 –

2.92 (m, 2H), 2.41 – 2.35 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 199.3, 137.3, 137.0, 133.0,

128.6, 128.0, 115.2, 37.7, 28.1. HRMS (ESI) m/z calcd. for C11H12NaO [M + Na+] 183.0778,

found 183.0780.


1-(4-Fluorophenyl)pent-4-en-1-one (4b)

Reaction performed with 2-chloro-1-(4-fluorolphenyl)ethanone 1b (171.6 mg,

0.99 mmol, 1 equiv.) and allyl alcohol (1 mL, 14.6 mmol, 15 equiv.). The residue was

purified by column chromatography on silica gel (eluent: cyclohexane/AcOEt = 90/10) and

yielded 115 mg (65%) of the expected product 4b as a yellow oil.

Data for 4b:

IR (ATR Diamond): 3076, 2924, 2358, 1686, 1598, 1506, 1411, 1361, 1230, 1156, 984, 916,

841 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.01 – 7.98 (m, 2H), 7.16 – 7.10 (m, 2H), 5.90 (ddt,

J = 16.9, 10.2, 6.5 Hz, 1H), 5.09 (dq, J = 17.2, 1.6 Hz, 1H), 5.02 (dd, J = 10.2, 1.3 Hz, 1H),

10 Y. Zhang and T. Rovis, J. Am. Chem. Soc. 2004, 126, 15964.


14

3.05 (t, J = 7.3 Hz, 2H), 2.53 – 2.47 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 197.8, 165.8 (d,

J = 254.5 Hz), 137.2, 133.4, 130.7 (d, J = 9.2 Hz), 115.7 (d, J = 38.8 Hz), 115.6, 37.7, 28.2.

HRMS (ESI) m/z calcd. for C11H11FNaO [M + Na+] 201.06861, found 201.06839.

1-(4-Chlorophenyl)pent-4-en-1-one (4c)

Reaction performed with 2-chloro-1-(4-chlorophenyl)ethanone 1c (190.3 mg, 1.01

mmol, 1 equiv.) and allyl alcohol (1 mL, 14.6 mmol, 15 equiv.). The residue was purified by

column chromatography on silica gel (eluent: cyclohexane/AcOEt = 90/10) and yielded 112

mg (57%) of the expected product 4c as a yellow oil.

Data for 4c:

IR (ATR Diamond): 3076, 2919, 2358, 1687, 1643, 1403, 1206, 1093, 980, 915, 834 cm-1; 1H

NMR (400 MHz, CDCl3) δ 7.91 – 7.88 (m, 2H), 7.45 – 7.41 (m, 2H), 5.89 (ddt, J = 16.8, 10.2,

6.5 Hz, 1H), 5.09 (dq, J = 17.1, 1.6 Hz, 1H), 5.02 (dq, J = 10.2, 1.3 Hz, 1H), 3.06 – 3.02 (m,

2H), 2.52 – 2.46 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 198.2, 139.5, 137.1, 135.3, 129.5,

129.0, 115.5, 37.8, 28.1. HRMS (ESI) m/z calcd. for C11H11ClNaO [M + Na+] 217.03906,

found 217.03879.


4-Pent-4-enoylbenzonitrile (4d)

Reaction performed with 4-(2-chloroacetyl)benzonitrile 1d (166.7 mg, 0.92 mmol,

1 equiv.) and allyl alcohol (1 mL, 14.6 mmol, 15 equiv.). The residue was purified by column

chromatography on silica gel (eluent: pentane/CH2Cl2 = 20/80) but afforded a mixture of the

product 4d and 4-acetylbenzonitrile. 1H NMR with butadiene sulfone as internal standard

allows to calculate 51 mg (30%) of the expected product 4d.


15

Data for 4d:



6.5 Hz, 1H), 5.09 (dq, J = 17.1, 1.6 Hz, 1H), 5.03 (dq, J = 10.2, 1.2 Hz, 1H), 3.09 (t, J = 7.3 Hz,

2H), 2.54 – 2.48 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 198.1, 134.0, 136.8, 132.6, 128.6,

118.4, 116.5, 115.9, 38.2, 27.9. HRMS (ESI) m/z calcd. for C12H11NNaO [M + Na+] 208.07329,

found 208.07308.


Methyl 4-pent-4-enoylbenzoate (4e)

Reaction performed with methyl 4-(2-chloroacetyl)benzoate 1e (212.9 mg, 1.00


column chromatography on silica gel (eluent: pentane/CH2Cl2 = 20/80) and yielded 87 mg

(40%) of the expected product 4e as a yellow powder.

Data for 4e:

IR (ATR Diamond): 3077, 2956, 1718, 1675, 1568, 1568, 1432, 1274, 1195, 1104, 755 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.6 Hz, 2H), 8.01 (d, J = 8.6 Hz, 2H), 5.91 (ddt, J

= 16.8, 10.2, 6.5 Hz, 1H), 5.10 (dq, J = 17.1, 1.6 Hz, 1H), 5.03 (dq, J = 10.2, 1.3 Hz, 1H), 3.96

(s, 3H), 3.11 (t, J = 7.3 Hz, 2H), 2.54 – 2.49 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 199.0,

166.3, 140.2, 137.1, 133.9, 129.9, 128.0, 115.6, 52.6, 38.2, 28.1. HRMS (ESI) m/z calcd. for

C13H14NaO3 [M + Na+] 241.08323, found 241.08352. M.p. = 73 °C.

11 D. M. Hodgson, P. G. Humphreys, S. M. Miles, C. A. J. Brierley, and J. G. Ward, J. Org. Chem., 2007, 72, 10009.


16

1-(4-tert-Butylphenyl)pent-4-en-1-one (4f)

Reaction performed with 2-chloro-1-(4-tert-butylphenyl)ethanone 1f (212.9 mg,

1.01 mmol, 1 equiv.) and allyl alcohol (1 mL, 14.6 mmol, 15 equiv.). The residue was purified

by column chromatography on silica gel (eluent: cyclohexane/AcOEt = 90/10) and yielded

118 mg (54%) of the expected product 4f as a yellow oil.

Data for 4f:


(400 MHz, CDCl3) δ 7.93 – 7.90 (m, 2H), 7.50 – 7.47 (m, 2H), 5.92 (ddt, J = 16.8, 10.2, 6.5

Hz, 1H), 5.10 (dq, J = 17.1, 1.6 Hz, 1H), 5.02 (dq, J = 10.2, 1.3 Hz, 1H), 3.08 – 3.05 (m, 2H),

2.54 – 2.48 (m, 2H), 1.35 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 199.2, 156.8, 137.5, 134.5,

128.1, 125.6, 115.3, 37.7, 35.2, 31.2, 28.3. HRMS (ESI) m/z calcd. for C15H20NaO [M + Na+]

239.14064, found 239.14067.

1-p-Tolyl-pent-4-en-1-one (4g)

Reaction performed with 2-chloro-1-p-tolylethanone 1g (170.2 mg, 1.00 mmol, 1

equiv.) and allyl alcohol (1 mL, 14.6 mmol, 15 equiv.). The residue was purified by column

chromatography on silica gel (eluent: cyclohexane/CH2Cl2 = 20/80) and yielded 77 mg (44%)

of the expected product 4g as a yellow oil.

Data for 4g:


NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 5.92 (ddt, J =

16.8, 10.2, 6.5 Hz, 1H), 5.09 (dq, J = 17.1, 1.6 Hz, 1H), 5.02 (dq, J = 10.2, 1.3 Hz, 1H), 3.08 –

3.04 (m, 2H), 2.53 – 2.47 (m, 2H), 2.42 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 199.2, 143.8,


17

137.5, 134.6, 129.4, 128.3, 115.3, 37.7, 28.4, 21.7. HRMS (ESI) m/z calcd. for C12H14NaO

[M + Na+] 197.09369, found 197.09368.


1-(4-Methoxyphenyl)pent-4-en-1-one (4h)

Reaction performed with 2-chloro-1-(4-methoxyphenyl)ethanone 1h (184 mg,


by column chromatography on silica gel (eluent: cyclohexane/AcOEt = 90/10) and yielded

146 mg (77%) of the expected product 4h as a yellow oil.

Data for 4h:

IR (ATR Diamond): 3074, 2928, 2843, 1676, 1601, 1511, 1256, 1172, 1028, 836 cm-1; 1H


6.5 Hz, 1H), 5.08 (dq, J = 17.1, 1.6 Hz, 1H), 5.00 (dd, J = 10.2, 1.5 Hz, 1H), 3.86 (s, 3H), 3.03

– 3.00 (m, 2H), 2.51 – 2.45 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 198.1, 163.5, 137.6,

130.4, 130.1, 115.2, 113.8, 55.5, 37.5, 28.5. HRMS (ESI) m/z calcd. for C12H14NaO2 [M +

Na+] 213.08860, found 213.08858.


1-(3-Fluorophenyl)pent-4-en-1-one (4i)

Reaction performed with 2-chloro-1-(3-fluorophenyl)ethanone 1i (193.4 mg, 1.12


12 S. Hok and N. E. Schore, J. Org. Chem., 2006, 71, 1736.

.


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column chromatography on silica gel (eluent: cyclohexane/AcOEt = 95/5) and yielded 73 mg

(37%) of the expected product 4i as a yellow oil.

Data for 4i:


NMR (400 MHz, CDCl3) δ 7.74 (ddd, J = 7.8, 1.4, 1.1 Hz ,1H), 7.65 (ddd, J = 9.5, 2.5, 1.6

Hz, 1H), 7.45 (td, J = 7.9, 5.5 Hz, 1H), 7.32 – 7.22 (m, 1H), 5.90 (ddt, J = 16.8, 10.2, 6.5 Hz,

1H), 5.10 (dq, J = 17.1, 1.6 Hz, 1H), 5.03 (dq, J = 10.2, 1.3 Hz, 1H), 3.08 – 3.05 (m, 2H), 2.54

– 2.48 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 198.2, 163.0 (d, J = 247.9 Hz), 139.1 (d, J =

6.1 Hz), 137.1, 130.4 (d, J = 7.6 Hz), 123.9 (d, J = 3.0 Hz), 120.1 (d, J = 21.5 Hz), 115.6,

114.9 (d, J = 22.3 Hz), 38.0, 28.1. HRMS (ESI) m/z calcd. for C11H11FNaO [M + Na+]

201.06861, found 201.06835.


1-(3-Methoxyphenyl)pent-4-en-1-one (4j)

Reaction performed with 2-chloro-1-(3-methoxyphenyl)ethanone 1j (185 mg, 1.00



(37%) of the expected product 4j as a yellow oil.

Data for 4j:

IR (ATR Diamond): 3075, 2938, 2841, 2358, 1685, 1589, 1432, 1260, 1171, 1039, 914, 874,

780 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.56 – 7.49 (m, 2H), 7.37 (t, J = 7.9 Hz, 1H), 7.11

(ddd, J = 8.2, 2.7, 0.9 Hz, 1H), 5.91 (ddt, J = 16.8, 10.2, 6.5 Hz, 1H), 5.09 (dq, J = 17.1, 1.6

Hz, 1H), 5.02 (dq, J = 10.2, 1.3 Hz, 1H), 3.86 (s, 3H), 3.08 – 3.05 (m, 2H), 2.53 – 2.47 (m,

2H). 13C NMR (101 MHz, CDCl3) δ 199.3, 159.9, 138.4, 137.4, 129.6, 120.7, 119.5, 115.4,


19

112.4, 55.5, 37.9, 28.3. HRMS (ESI) m/z calcd. for C12H14NaO2 [M + Na+] 213.08860, found

213.08844.


1-(2,4-Dichlorophenyl)pent-4-en-1-one (4k)

Reaction performed with 2-chloro-1-(2,4-dichlorophenyl)ethanone 1k (220.8 mg,


by column chromatography on silica gel (eluent: cyclohexane/AcOEt = 90/10) and yielded 81

mg (36%) of the expected product 4k as a yellow oil.

Data for 4k:

IR (ATR Diamond): 3079, 2923, 2358, 1696, 1582, 1372, 1272, 1200, 1104, 982, 915, 820

cm-1; 1H NMR (400 MHz, CDCl3) δ 7.45 – 7.42 (m, 2H), 7.32 (dd, J = 8.3, 2.0 Hz, 1H), 5.86

(ddt, J = 16.8, 10.2, 6.5 Hz, 1H), 5.10 – 5.00 (m, 2H), 3.04 (t, J = 7.3 Hz, 2H), 2.50 – 2.45 (m,

2H). 13C NMR (101 MHz, CDCl3) δ 201.4, 137.7, 137.4, 136.7, 132.1, 130.5, 130.2, 127.4,

115.8, 42.1, 28.2. HRMS (ESI) m/z calcd. for C11H10Cl2NaO [M + Na+] 250.99991, found

251.00009.

1,2-Diphenylpent-4-en-1-one (4l)

Reaction performed with 2-chloro-1,2-diphenylethanone 1l (230.1 mg, 1.00 mmol,

1 equiv.) and allyl alcohol (1 mL, 14.6 mmol, 15 equiv.). The residue was purified by column

chromatography on silica gel (eluent: cyclohexane/CH2Cl2 = 20/80) and yielded 77 mg (33%)

of the expected product 4l as a yellow oil.

13

L. E. Overman et A. E. Renaldo, J. Am. Chem. Soc., 1990, 112, 3945.


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Data for 4l:

IR (ATR Diamond): 3068, 2922, 2358, 1681, 1595, 1493, 1447, 1343, 1245, 1205, 1074, 993,

917, 753, 697 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.99 – 7.96 (m, 2H), 7.52 – 7.47 (m, 1H),

7.43 – 7.38 (m, 2H), 7.30 – 7.32 (m, 4H), 7.24 - 7.20 (m, 1H), 5.77 (ddt, J = 17.1, 10.2, 6.9

Hz, 1H), 5.06 (dq, J = 17.1, 1.5 Hz, 1H), 4.99 (ddt, J = 10.2, 2.0, 1.1 Hz, 1H), 4.65 (t, J = 7.3

Hz, 1H), 2.97 (dddt, J = 14.5, 7.9, 6.9, 1.2 Hz, 1H), 2.59 (dtt, J = 14.3, 6.9, 1.3 Hz, 1H). 13C

NMR (101 MHz, CDCl3) δ 199.3, 139.2, 136.8, 136.1, 133.0, 129.0, 128.8, 128.6, 128.3,

127.2, 116.8, 53.7, 38.3. HRMS (ESI) m/z calcd. for C17H16NaO [M + Na+] 259.10934, found

259.10973.

4-Methyl-1-phenylpent-4-en-1-one (4p, 4q)

Reaction performed with α-chloroacetophenone 1a (77.4 mg, 0.50 mmol, 1 equiv.)

and, (E)-but-2-en-1-ol (1.3 mL, 15.2 mmol, 30 equiv.). The residue was purified by column

chromatography on silica gel (eluent: pentane/CH2Cl2 = 90/10) and yielded 44 mg (50%) of a

mixture (80/20) of the linear 4p and the branched products 4q as a yellow oil.

Data for 4p, 4q:

IR (ATR Diamond): 2924, 2856, 1733, 1687, 1594, 1448, 1364, 1264, 1205, 968 cm-1; 1H

NMR (400 MHz, CDCl3) δ 7.98 – 7.95 (m, 2H (4p) + 2H (4q)), 7.58 – 7.54 (m, 1H (4p) + 1H

(4q)), 7.49 – 7.45 (m, 2H (4p) +2H (4q)), 5.86 (ddd, J = 17.0, 10.4, 6.4 Hz, 1H (4q)), 5.52-

5.50 (m, 2H (4p)), 5.04 (dt, J = 17.3, 1.3 Hz, 1H (4q)), 4.99 – 4.94 (m, 1H (4q)), 3.06 – 3.02

(m, 2H (4p) + 1H (4q)), 2.94 – 2.88 (m, 1H (4q)), 2.50 (m, 1H (4q)), 2.46 – 2.40 (m, 2H

(4p)), 1.64-1.66 (m, 3H (4p)), 1.11 (d, J = 6.4 Hz, 3H (4q)). 13C NMR (101 MHz, CDCl3) δ

199.9, 196.4, 143.2, 137.1, 133.0, 133.0, 130.1, 129.9, 128.7, 128.2, 128.1, 126.0, 113.1, 45.3,

38.7, 33.7, 27.3, 19.9, 18.0. HRMS (ESI) m/z calcd. for C12H14NaO [M + Na+] 197.09369,

found 197.09358.


21

4-Methyl-1-phenylpent-4-en-1-one (4r)

Reaction performed with α-chloroacetophenone 1a (78.1 mg, 0.50 mmol, 1 equiv.)

and 2-methylprop-2-en-1-ol (1.3 mL, 15.4 mmol, 30 equiv.). The residue was purified by


(51%) of the expected product 4r as a yellow oil.

Data for 4r:

IR (ATR Diamond): 2924, 2853, 2360, 2341, 1725, 1686, 1650, 1558, 1448, 1360, 1202, 967,

888 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.99 – 7.97 (m, 2H), 7.59 – 7.54 (m, 1H), 7.49 – 7.45

(m, 2H), 4.77 (s, 1H) 4.72 (s, 1H), 3.15 – 3.11 (m, 2H), 2.48 – 2.44 (m, 2H), 1.79 (s, 3H). 13C

NMR (101 MHz, CDCl3) δ 199.8, 144.8, 137.1, 133.1, 128.7, 128.1, 110.3, 36.9, 32.0, 22.8.

HRMS (ESI) m/z calcd. for C12H14NaO [M + Na+] 197.09369, found 197.09363.


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